Clinical Significance of Upfront Ibrutinib in CLL

Javier Pinilla-Ibarz, MD, PhD: The introduction of ibrutinib, a BTK inhibitor, has completely changed the paradigm for the treatment of chronic lymphocytic leukemia. In fact, as I mentioned before, patients with 17p deletion should receive ibrutinib, which right now is the best therapy for this high-risk population. However, it is important to point out that ibrutinib works independently of any prognostic marker and in this case, any high-risk prognostic markers such as 17p-, IGVH unmutated immunoglobulin, or even complex cytogenetics. Even more recently in 11q, the classically unfavorable prognostic factor, we know that this drug also has very good activity.

The bottom line is this drug works independently in any high-risk prognostic feature. However, it is true that sometimes in the long run, the people who really fail this therapy, after sometimes years of therapy, used to be or tend to be the people who really carry over these high prognostic features. But right now, to start with, this drug really produces a very long-term remission in a very high category of patients.

The RESONATE-2 trial compared the use of ibrutinib, a BTK inhibitor, against chlorambucil, an old chemotherapy drug also administered orally to patients with chronic lymphocytic leukemia. This trial was designed to be tested in older patients with comorbid conditions. However, one important point to take into consideration is that this trial did not include patients with 17p-, as mentioned before, patients with a very high-risk category or very high-risk prognosis in terms of therapy. The trial shows us significant difference in progression-free survival with chemotherapy and right now, it has become category 1 by the NCCN.

We know that this trial, right now, is almost 3 years of follow-up, includes around 126 patients, and it is remarkable to really see the long-term results. We saw that around 5 patients progressed after 3 years of therapy, which, in my opinion, is a remarkable outcome. However, a few other patients in general, 10% to 15% at this point after 3 years of follow-up, have discontinued the drug secondary to side effects, even acute and mostly chronic side effects produced by the drug. Overall, the progression-free survival of this trial is not being reached and continues to be followed. And I think we’re going to really continue these good results for a long period of time.